Process for the production of 2-nitrobutylmorpholine

ABSTRACT

In a process for the production of 2-nitrobutylmorpholine from 1-nitropropane, morpholine and formaldehyde the improvement comprising mixing 1-nitropropane and morpholine, heating to about 55-60° C., adding formaldehyde over about a 3-4 hour period, holding the reaction mixture at about 55-60° C. for about a 2-3 hour period to make a total addition/holding period of at least six hours, cooling the reacton mixture to form a two phase oil/aqueous system and concentrating the oil layer to 2-nitrobutylmorpholine by removing excess water and 1-nitropropane.

This is a continuation of copending application Ser. No. 741,175, filed Nov. 12, 1976.

BACKGROUND OF THE INVENTION

This invention relates to an improved process for the production of 2-nitrobutylmorpholine.

More particularly, this invention relates to an improved process for the production of 2-nitrobutylmorpholine by reacting 1-nitropropane, morpholine and formaldehyde.

The prior known processes for the production of 2-nitrobutylmorpholine, Senkus, U.S. Pat. No. 2,474,791 teach the production of 2-nitroisobutylmorpholine from the reaction of a nitroalcohol and a cyclic secondary amine (2-nitro-2-methyl-1-propanol and morpholine). The second process taught by Senkus is the reaction of formaldehyde with the cyclic secondary amine (morpholine) which in turn is reacted with a secondary nitroparaffin (2-nitropropane). A variation of the first method as taught by Senkus is the reaction of formaldehyde with the nitroparaffin (2-nitropropane) to produce the nitroalcohol which in turn is reacted with the cyclic secondary amine (morpholine) which process is hereinafter called the morpholine addition method.

A by-product from the reaction forming 2-nitrobutylmorpholine from 1-nitropropane, formaldehyde and morpholine is 2-nitro-1-butanol. 2-Nitro-1-butanol is difficult to separate from the 2-nitrobutylmorpholine product and as a nitroalcohol can react violently with bases such as morpholine. The 2-nitro-1-butanol formed contaminates and reduces the yield and purity of 2-nitrobutylmorpholine. Another disadvantage inherent in the prior processes is that they require excess 1-nitropropane and morpholine to drive the reaction to completion. Generally a 20% excess 1-nitropropane and 1% excess morpholine over formaldehyde are required. The use of such excesses is uneconomical and the excess of both reactants adds to the contamination of the product. The use of excess reactants reduces the efficiency of the process in that more reactants are required to drive the reaction to completion than actually react and effort is needed to separate the reactants from the finished products. The prior processes require strict controls during the reaction in order to produce 2-nitrobutylmorpholine efficiently. In the morpholine addition process strict controls are maintained on the addition of the morpholine. Longer addition times than three hours or interruptions during the addition step produces more of the by-product 2-nitro-1-butanol.

SUMMARY OF THE INVENTION

It is an object of this invention to provide an improved process for the production of 2-nitrobutylmorpholine.

Another object of this invention is to provide an improved process for the production of 2-nitrobutylmorpholine by reacting 1-nitropropane, morpholine and formaldehyde.

A further object of this invention is to provide an improved process for the production of 2-nitrobutylmorpholine wherein the product produced is of greater purity than that from prior known processes.

Other objects of this invention will be apparent to those skilled in the art from the disclosure herein.

An improvement has been found in the process for the production of 2-nitrobutylmorpholine from the reaction of 1-nitropropane, morpholine and formaldehyde in about a 1:1:1 molar ratio. According to the prior process, the 1-nitropropane and formaldehyde were mixed together at about 50°-60° C. then morpholine was added over a 1-3 hour addition time. According to the present invention, the improvement comprises mixing 1-nitropropane and morpholine, heating to about 55°-60° C., then adding formaldehyde over about a 3-4 hour period, holding the reaction mixture at about 55°-60° C. for about a 2-3 hour period to make a total addition/holding period of at least six hours, cooling the reaction mixture to form a two phase oil/aqueous system and concentrating the oil layer to 2-nitrobutylmorpholine by removing excess water and 1-nitropropane.

DETAILED DISCUSSION

The process of this invention is an improvement over the prior processes for the production of 2-nitrobutylmorpholine. The prior processes teach mixing (1) 2-nitro-2-methyl-1-propanol and morpholine, or (2) mixing morpholine and formaldehyde then adding 1-nitropropane or (3) mixing formaldehyde and 1-nitropropane then adding morpholine. The improved process of this invention mixes the reactants, 1-nitropropane and morpholine, then adds formaldehyde. The unexpected result was obtained that the process of this invention produces a product of greater purity than the prior processes. The process produces less contaminating by-products and is less sensitive to longer addition times or interruptions during the addition step. The process of this invention produces a product, 2-nitrobutylmorpholine, that is essentially free from the major contaminant of the prior known processes, 2-nitro-1-butanol.

1-Nitropropane and morpholine are charged to a reaction vessel equipped with a jacket for heating or cooling. An excess of 5-20% 1-nitropropane, preferably 10-15% over a 1:1 molar ratio to formaldehyde is charged to the reaction vessel. The preferred range of 1-nitropropane is sufficient to produce high yields, but small enough to leave little unreacted 1-nitropropane to contaminate the product, 2-nitrobutylmorpholine. Also, the 10-15% excess 1-nitropropane does not produce any appreciable amount of 2-nitro-1-butanol by-product.

The morpholine is added to the reaction vessel preferably in about a 1% excess over the 1:1 molar ratio to formaldehyde. Amounts less than 1% excess produce 2-nitro-1-butanol and amounts greater than 1% decrease the product purity by leaving unreacted morpholine in the end product.

The mixture of 1-nitropropane and morpholine is heated to between 55°-60° C. Temperatures lower than 55° C. do not produce 2-nitrobutylmorpholine efficiently. Temperatures greater than 60° C. are not detrimental to product composition, but can lead to high coloration of the product.

Formaldehyde, 37%, is added to the vessel with constant agitation and maintaining the temperature within the preferred 55°-60° C. range. The formaldehyde is added over a 21/2-6 hour addition period. Preferably, the formaldehyde is added in about 3-4 hours addition time. Addition times of less than 21/2 hours produce, 4,4'-(2-ethyl-2-nitrotrimethylene)dimorpholine and addition times of longer than 6 hours have no appreciable effect on product formation. Longer addition times than 6 hours and interruptions during addition produce no deleterious effects on the product quality or yield of the 2-nitrobutylmorpholine. The reaction mixture is held at the preferred temperature for a combined addition and holding period of 41/2-8 hours. Preferably, the reaction mixture is held for a minimum of two hours after the addition of the formaldehyde. During the holding period, the reaction goes to completion and any of the dimorpholine product formed converts to 2-nitrobutylmorpholine.

After the holding period, the reaction mixture is cooled to less than 30° C. Upon cooling the reaction mixture separates into oil and water layers. The water (upper) layer is separated and discarded. The oil layer is the product 2-nitrobutylmorpholine. The oil layer is concentrated to remove excess 1-nitropropane and other volatile or soluble materials, either by steam sparging or azeotropic removal with water. If to be performed after layer separation, generally an 8-hour period is allowed for the mixture to stand quietly to promote separation of the layers. However, this 8-hour separation period can be eliminated by steam sparging without layer separations. When the steam sparging method is used, about 0.7 to 1 pound of steam per pound of 1-nitropropane charged is sparged. During steam sparging, the water layer (if not separated) and any other water or volatile material is volatilized, collected and discarded. When the concentrating method is by azeotropic removal with water, the amount of water used is 200% of the excess 1-nitropropane charged and distillation at reduced pressure (77 mm Hg Absolute) is conducted at 90° C. The amount of water present can be from the 37% formaldehyde in the initial charge, thus avoiding losses due to layer separation technique or product solubility in the water layer. The water azeotropic removal method removes 1-nitropropane from the 2-nitrobutylmorpholine.

The oil layer is the product, 2-nitrobutylmorpholine, and is further purified by stripping dry by distillation to remove any remaining water. The 2-nitrobutylmorpholine formed by the process of this invention has less contaminants than that formed by the prior processes and is essentially free from the by-product 2-nitro-1-butanol.

The process of this invention will be better understood with reference to the following examples. It is understood that these examples are intended for illustration only and it is not intended that the invention be limited thereby.

EXAMPLE 1

To a 400-gallon glass-lined, agitated and jacketed vessel was charged 1,115 lbs 1-nitropropane (12.5 lb-moles) and 918 lbs morpholine (10.6 lb-moles). The vessel was jacketed for heating and was equipped with a distillate condenser head. The vessel was also equipped with a steam line for blowing steam into the vessel from the bottom for steam sparging. The mixture was heated to 58°-60° C. by steam heating. To the vessel was charged 847 lbs of 37% formaldehyde (10.5 lb-moles) over a period of four hours. The reaction materials were held for another two hours at 58°-60° C. for a total of six hours to complete the reaction.

The reaction mixture was cooled to less than 30° C. and the two-phase system separated over an eight-hour period. The water (upper) layer was discarded. The oil (lower) layer was concentrated to 90° C. liquid temperature at 75 mm Hg absolute pressure by steam sparging to remove the excess 1-nitropropane and other volatile materials. About 0.7 to 1 pound of steam per pound of 1-nitropropane charged was sparged. The amount of sparge was determined by observing the amount of water collected.

The oil was stripped dry of water (0.5%) by distilling at 75 mm Hg and 90° C. liquid temperature for one hour. After drying, the product was cooled to less than 30° C. liquid temperature and transferred to containers.

The product, 2-nitrobutylmorpholine, 1,950 lbs (10.4 lb-moles), approximately 99% yield, was a light amber colored liquid, specific gravity (20/20° C.) 1.09 ± 0.02 and assayed 98.5%.

EXAMPLES 2-11

The process of Example 1 was repeated in all essential details with the exceptions that various formaldehyde addition times were used. Also, the method of concentrating the oil layer was varied from steam sparging to azeotropic removal with water. In Example 7 after a three-hour addition of one half the total formaldehyde charge there was a three hour interruption after which the remaining one half of the formaldehyde was added. In Examples 9 and 11 the azeotropic removal of excess 1-nitropropane was conducted using the water present from the initial 37% formaldehyde charge.

The results of the various runs are given in Table A, which gives the various reaction parameters of the examples plus the gas chromatographic analysis of the product formed.

                                      TABLE I                                      __________________________________________________________________________     Reaction Parameters and Vanderbilt G.C. Analysis.sup.(1)                                          Vanderbilt G.C. Area % Compositions                                            Elution Times (Minutes)                                                        .4-5 1.0   2.0  3.6                                                                               5.2                                                                               6.2   8.4                             HCHO               Identities                                                  Example                                                                             Addition                                                                            Concentration                                                                           Nitro-     2-Nitro-                                         Number                                                                              Time Method   paraffins                                                                           Morpholine                                                                           1-Butanol                                                                           .sup.(2)                                                                          .sup.(3)                                                                          Unknown                                                                              .sup.(4)                        __________________________________________________________________________     2    3    Steam Sparge                                                                            0.43 0.07  --   0.84                                                                              98.6                                                                              0.02  0.06                            3    3    H.sub.2 O Azeotrope                                                                     0.94 --    --   0.79                                                                              98.2                                                                              0.02  0.03                            4    3    H.sub.2 O Azeotrope                                                                     0.91 --    --   0.77                                                                              98.3                                                                              0.03  0.02                            5    3    H.sub.2 O Azeotrope                                                                     0.46 0.04  --   0.87                                                                              98.6                                                                              0.03  0.04                            6    6    Steam Sparge                                                                            0.29 0.09  --   0.83                                                                              98.7                                                                              0.03  0.07                            7      6.sup.(5)                                                                         Steam Sparge                                                                            0.46 --    --   0.89                                                                              98.5                                                                              0.03  0.11                            8    3    H.sub.2 O Azeotrope                                                                     0.57 0.09  --   0.81                                                                              98.5                                                                              0.02  0.05                            9    3    H.sub.2 O Azeotrope.sup.(6)                                                             0.60 0.15  --   0.87                                                                              98.3                                                                              0.03  0.03                            10   3    Steam sparge                                                                            0.50 --    --   0.80                                                                              98.5                                                                              --    0.20                            11   3    H.sub.2 O Azeotrope.sup.(6)                                                             0.80 --    --   0.90                                                                              98.2                                                                              --    0.20                            __________________________________________________________________________      .sup.(1) Examples 2-9 were with 20% excess 1-nitropropane, Examples 10 an      11 were with 10% excess 1-nitropropane                                         .sup.(2) 4-(2-methyl-2-nitropropy)morpholine                                   .sup.(3) 2-nitrobutylmorpholine                                                .sup.(4) 4,4'-(2-ethyl-2-nitrotrimethylene)dimorpholine.                       .sup.(5) 3 hour addition rate with 3 hour feed interruption at midpoint o      feed.                                                                          .sup.(6) Reaction H.sub.2 O layer not separated.                          

What is claimed is:
 1. In the process for the production of 2-nitrobutylmorpholine from 1-nitropropane, morpholine and formaldehyde in about a 1.05-1.2:1.01:1 molar ratio the improvement comprising the steps of (a) mixing 1-nitropropane, and morpholine, (b) heating the mixture to about 55°-60° C., (c) then adding formaldehyde over about a 3-4 hour period, (d) holding the mixture at about 55°-60° C. for about a 2-3 hour period to make a total addition/holding period of at least six hours, (e) cooling the reaction mixture to form a two-phase oil-aqueous system, (f) collecting and discarding the water (upper) layer and (g) concentrating the oil layer to 2-nitrobutylmorpholine by removing excess water and 1-nitropropane.
 2. The process of claim 1 wherein the formaldehyde is added over about a 3 hour period or more.
 3. The process of claim 1 wherein said concentrating of the oil layer is performed by steam sparging.
 4. The process of claim 1 wherein said concentrating of the oil layer is performed by extraction with water.
 5. The process of claim 1 wherein said formaldehyde is added over a four-hour period and said mixture is held at 55°-60° C. for a two-hour period. 